The use of amphiphilic compounds as a drug delivery system is well known in the state of the art (cf. U.S. Pat. No. 5,650,393; U.S. Pat. No. 5,688,761; U.S. Pat. No. 5,665,328; U.S. Pat. No. 5,124,081; U.S. Pat. No. 5,109,038). Formation of complexes in the form of micelles between surface-active substances and pharmaceutical agents is also known for example for improving the transdermal and transmembrane penetration of the active agent (Tomlinson and Davis, J. Colloid. Interf., Sci. 74 (1980) 349). It is also known that pharmaceutical agents usually have better transport properties through biological membranes in their non-ionized form than in the ionized state (Cools and Jansen, J. Pharm. Pharmacol. 35 (1983) 689-691). It is also known that peptides which are present in a multiple ionized form at physiological pH values, are also not optimal for transport to the site of action (drug delivery) since charged molecules and in particular polypeptides have a low solubility in lipids (Hirai et al., Int. J. Pharm. 7 (1991) 317-325). It is known from Okada et al., J. Pharm. Sci. 72 (1993) 75-78 that it is advantageous to bind a lipophilic counterion to the ionic part of the agent and thus improve the interaction with the biological membrane in order to facilitate transport of proteins through intestinal membranes. For example Hazzenga and Berner describe an improved method for the transdermal transport of zwitterionic active agents in J. Controlled Release 16 (1991) 77-88.
Other methods for improving the interaction of agents with biological membranes are described for example by Lee et al., Critical Rev. Therp. Drug Carrier Systems 8 (1991) 91-192, Morimoto et al., Arch. Int. Pharmacodyn. 302 (1989) 18-26 and Aungst, Int. J. Pharm. 33 (1986) 225-234. However, in all these methods the aim was to increase the hydrophobicity of the active agent in order to facilitate its penetration through biological membranes such as skin and deliver said agent into the cell. The surface-active substances are used for this at a concentration which was above the critical micelle concentration (CMC, Womack et al., Biochim. Biophys. Acta 733 (1983) 210). A disadvantage of such methods is that the high concentrations of the surface-active substances that are used have a massive influence on the cell membrane and may damage it.
It is known from WO 94/08599 that a homogeneous solution of an active agent can be prepared for the production of carrier-bound active agents by adding an adequate amount of an anionic detergent to form a precipitate, isolating the precipitate and dissolving it again in an organic solvent. This homogeneous solution which contains a complex between the anionic detergent and the active agent can then be used to embed or disperse the active agent in a solid matrix. In addition WO 94/08599 mentions that a complex of the protein with an anionic detergent can be formed and the active agent can be released from it for the controlled release of a protein.
It is known that the activity of proteins can be improved by covalent coupling to hydrophobic compounds such as fatty acids or steroids. However, such methods are complicated and lead to inhomogeneous products due to the chemical reaction of the coupling (cf. e.g. Ekrami, H. M. et al., FEBS Letters 371 (1995) 283-286, Pepinski, R. B. et al., J. Biol. Chem. 273 (1998) 14037-14045).